RESUMO
Paravulvus zhongshanensis sp. nov., isolated from soil in a location at Jiangsu Province, China, is described and illustrated based on morphological, morphometric and molecular characterizations. The new species is characterized by its body 1.17-1.53 mm long, lip region offset by marked constriction and 12.1-13.8 µm broad, mural tooth deltoid and 9.6-11.7 µm long, neck 278-360 µm long, pharyngeal expansion 164-208 µm long or occupying more than one-half (54-62%) of total neck length, uterus 32.5-35.3 µm long or 1.0-1.1 times the corresponding body diameter, V = 47.8-53.4, paravulvae absent, female tail subcylindrical conoid (30.5-39.5 µm, c = 36.0-45.5, c' = 1.7-2.2) with widely rounded end, and male unknown. The new species was compared with six known species of the genus including Paravulvus acuticaudatus, Paravulvus confusus, Paravulvus hartingii, Paravulvus iranicus, Paravulvus loofi and Paravulvus microdontus mainly by similarities in having conical tail and c' value larger than 1.3. The rRNA and mitochondrial cytochrome oxidase subunit 1 genes of the new species were obtained and were used for reconstructing the phylogenetic relationships of the new species.
Assuntos
Helmintos , Nematoides , Animais , Masculino , Feminino , Filogenia , Helmintos/genética , RNA Ribossômico , ChinaRESUMO
Objective: To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test. Results: A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance. Conclusion: Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log(10)IU/ml), HBsAg level at 24 weeks (≤ 0.92 log(10)IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log(10)IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log(10)IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.
Assuntos
Hepatite B Crônica , Interferon-alfa , Polietilenoglicóis , Humanos , Lactente , DNA Viral , Antígenos E da Hepatite B , Antígenos de Superfície da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêuticoRESUMO
AIM: To profile molecular changes in lipopolysaccharide (LPS)-induced experimental pulpitis in a rat model and explore the feasibility of a molecular-based diagnostic strategy for pulpitis. METHODOLOGY: Seventy-three maxillary incisors of Sprague-Dawley rats were used to establish pulpitis models with LPS. Inflammatory grading was performed in four equal sections of the pulp divided from the injured site to the root apex. An antibody array was used to compare the expression of 67 molecules between control pulp and inflamed pulp 12 and 72 h after LPS application. The levels of differentially expressed molecules in the control and inflamed pulp (collected at 3, 6, 9, 12, 24 and 72 h after LPS treatment) were examined via ELISA, and correlations between inflammatory scores and molecule expression were assessed. The molecule distributions in the pulp were investigated by immunofluorescence staining. Data were analysed with paired t-test, one-way anova, Kruskal-Wallis tests, and Spearman's and Pearson's correlations with significance set at P < 0.05. RESULTS: Polymorphonuclear neutrophils were observed in the injured site 3 h after LPS stimulation. Inflammatory infiltration peaked at 12 h and was limited to the injured site with osteodentine deposition at 72 h. Thirteen molecules were significantly differentially expressed between the control and LPS-injured pulp. ELISA validated that tissue inhibitor of metalloproteinase-1 (TIMP-1) expression dramatically peaked at 12 h (compared with other time points, P < 0.05) and returned to baseline at 72 h. The TIMP-1 concentration was strongly correlated with inflammation severity in the apical three-quarters of the pulp, and the strongest correlation was found in the lower-middle quarter (r = 0.786, P < 0.001). Immunofluorescence staining revealed that in the apical three-quarters of the pulp, TIMP-1 expression was significantly higher in the 12 h group than in the control and 3, 6, 24 and 72 h groups (P < 0.01). CONCLUSION: This study provides a molecular profile of LPS-induced pulpitis in a rat model. TIMP-1 had a strong positive correlation with the severity of dental pulp inflammation, verifying the feasibility of applying biomarkers to identify specific pathological conditions in pulpitis.
Assuntos
Pulpite , Animais , Biomarcadores , Polpa Dentária , Mediadores da Inflamação , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1RESUMO
AIM: To evaluate the efficacy and to identify prognostic factors of polyvinyl alcohol (PVA) chemoembolisation for treating advanced hepatocellular carcinoma (HCC) with portal vein (PV) tumour thrombosis (PVTT) and arterioportal shunts. MATERIALS AND METHODS: The clinical data of 145 advanced HCC patients with PVTT and arterioportal shunts were collected. The patients were divided into two groups: group A, with main PV invasion, (n=56) and group B, with PV branch invasion, (n=89). Based on arterioportal shunt types, different particle sizes of PVA were used for chemoembolisation. The overall survival (OS), time to progression (TTP), and postoperative complications were analysed retrospectively. RESULTS: The median OS of all patients was 10.1 months. The median OS of group A and group B was 8.2 and 12.5 months, respectively (χ2=6.03, p=0.01). The overall 6-, 12-, and 18-month survival rates of groups A and B were 63.8%, 24.9%, and 6.3%, and 78.1%, 55.2%, and 23.7%, respectively. After embolisation, there were two cases of acute liver failure and three cases of upper gastrointestinal bleeding. Cox multivariate survival analysis revealed that main PVTT (HR [hazard ratio]=1.75, p=0.01), Child-Pugh B class (HR=1.99, p=0.003) and tumour burden ≥50% (HR=3.25, p<0.001) were independent risk factors. A dose of oxaliplatin >100 mg (HR=0.48, p<0.001) was an independent protection factor. CONCLUSION: Treatment of advanced HCC with PVTT and arterioportal shunts by PVA chemoembolisation is safe and effective. The patients achieved a better prognosis with the dose of oxaliplatin >100 mg, while main PVTT, Child-Pugh B class, and tumour burden ≥50% were poor prognostic indicators.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Álcool de Polivinil/uso terapêutico , Veia Porta/patologia , Trombose Venosa/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa/patologiaRESUMO
Objective: To investigate the clinical effect of polyvinyl alcohol (PVA) particles combined with chemoembolization using chemotherapeutic agents or chemotherapeutic agents lipiodol emulsion (CALE) in the treatment of hepatocellular carcinoma (HCC) complicated by hepatic arteriovenous shunt (HAVS) and related prognostic factors. Methods: A retrospective analysis was performed for the clinical data of 133 patients with HCC complicated by HAVS. HAVS was classified into slow-flow HAVS, intermediate-flow HAVS, and high-flow HAVS, which were treated with 300-500µm, 500-710µm, and 710-1000µm PVA particles, respectively. The patients with slow-flow and intermediate-flow HAVS underwent embolization with PVA combined with chemotherapeutic agents followed by CALE, while those with high-flow HAVS underwent the treatment with PVA combined with chemotherapeutic agents alone. The survival time, progression-free survival time, and postoperative complications were followed up and analyzed. The Kaplan-Meier method was used to calculate cumulative survival rate and the Cox proportional hazards model was used to determine prognostic factors. Results: The median overall survival (OS) of 133 patients was 9.1 months, and the 6-, 12-, and 24-month survival rates were 73.7%, 36.2%, and 10.2%, respectively. The median OS of slow-flow group (36 patients), intermediate-flow group (58 patients), and high-flow group (39 patients) were 7.3, 9.1, and 10.8 months, respectively. And the 6- and 12-month survival rates were 69.2%/19.0%, 72.4%/39.2%, and 77.8%/42.7%, respectively. There was no significant difference in survival time between the patients with different types of HAVS (χ2= 2.865,P= 0.239). The incidence rates of postoperative gastroesophageal variceal bleeding and acute liver failure were 1.1% and 0.4%, respectively. The results of Cox regression analysis showed that preoperative alpha-fetoprotein level≥400 ng/ml (HR= 2.105,P= 0.006) was an independent risk factor, while multiple embolizations (HR= 0.482,P= 0.011), tumor remission (HR= 0.431,P= 0.041), and multimodality therapy (HR= 0.416,P= 0.004) were independent protective factors. Conclusion: PVA particles combined with chemotherapeutic agents or CALE is safe and effective in the treatment of HCC complicated by HAVS. Patients with multiple embolizations, tumor remission, and multimodality therapy tend to have good prognosis, while those with a high level of alpha-fetoprotein before embolization often have poor prognosis.
Assuntos
Derivação Arteriovenosa Cirúrgica , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Álcool de Polivinil/efeitos adversos , Fístula Arteriovenosa , Carcinoma Hepatocelular/patologia , Terapia Combinada , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/epidemiologia , Óleo Etiodado , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , alfa-FetoproteínasRESUMO
BACKGROUND AND OBJECTIVE: Periodontal diseases are often induced by periodontopathogens, which are always exposed to certain innate immune factors in gingival crevicular fluid, including human ß-defensin-2 (hBD-2). This study aims to investigate the relationship among periodontopathogens, clinical parameters and hBD-2 expression. MATERIAL AND METHODS: Thirty-two healthy controls, 42 patients with chronic gingivitis and 95 patients with chronic periodontitis were recruited in Guangxi, China. Bleeding index, probing depth and clinical attachment level were measured for all teeth including mesiobuccal, buccal, disobuccal, mesiolingual, lingual, disolingual six sites of all patient. Gingival crevicular fluid samples were collected from the study sites. The prevalence and copy numbers (CN) of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsythia and total bacteria in gingival crevicular fluid were quantified by real-time PCR. The hBD-2 concentration in gingival crevicular fluid was measured by ELISA. RESULTS: Both the prevalence and the CN of A. actinomycetemcomitans, P. gingivalis, T. denticola and T. forsythia were higher in patients with chronic periodontitis than in healthy controls and patients with chronic gingivitis; however, there was no significant difference in the prevalence of P. intermedia among the three study groups, and the highest CN was found in patients with chronic gingivitis, rather than in patients with chronic periodontitis. The loads of P. gingivalis, P. intermedia, T. denticola and total bacteria were positively related to probing depth, bleeding index and clinical attachment level. The concentration of hBD-2 in gingival crevicular fluid was higher in patients with chronic gingivitis and in patients with chronic periodontitis than in healthy controls. In addition, the hBD-2 concentration was positively related to the CN of P. gingivalis, T. forsythia and total bacteria, as well as to bleeding index and probing depth. CONCLUSION: The prevalence, composition and CN of periodontopathogens were closely related to the severity of periodontal disease, and the red complex was related to the severity of clinical symptoms of periodontal diseases. The concentration of hBD-2 in gingival crevicular fluid from periodontal disease sites was higher than that in gingival crevicular fluid from healthy sites, which suggests that hBD-2 expression might be up-regulated by periodontopathogens.
Assuntos
Periodontite Crônica/microbiologia , Líquido do Sulco Gengival/microbiologia , Gengivite/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , beta-Defensinas/análise , Adulto , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Carga Bacteriana , Bacteroides/imunologia , Bacteroides/isolamento & purificação , Periodontite Crônica/imunologia , Feminino , Líquido do Sulco Gengival/imunologia , Gengivite/imunologia , Bactérias Gram-Negativas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/imunologia , Perda da Inserção Periodontal/microbiologia , Índice Periodontal , Bolsa Periodontal/imunologia , Bolsa Periodontal/microbiologia , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/isolamento & purificação , Prevotella intermedia/isolamento & purificação , Treponema denticola/isolamento & purificação , Adulto JovemRESUMO
This paper reviews the recent research and development of clay-based polymer nanocomposites. Clay minerals, due to their unique layered structure, rich intercalation chemistry and availability at low cost, are promising nanoparticle reinforcements for polymers to manufacture low-cost, lightweight and high performance nanocomposites. We introduce briefly the structure, properties and surface modification of clay minerals, followed by the processing and characterization techniques of polymer nanocomposites. The enhanced and novel properties of such nanocomposites are then discussed, including mechanical, thermal, barrier, electrical conductivity, biodegradability among others. In addition, their available commercial and potential applications in automotive, packaging, coating and pigment, electrical materials, and in particular biomedical fields are highlighted. Finally, the challenges for the future are discussed in terms of processing, characterization and the mechanisms governing the behaviour of these advanced materials.
Assuntos
Silicatos de Alumínio/química , Técnicas Biossensoriais/métodos , Sistemas de Liberação de Medicamentos/métodos , Indústrias/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Polímeros/química , Silicatos de Alumínio/análise , Técnicas Biossensoriais/instrumentação , Argila , Cristalização/métodos , Sistemas de Liberação de Medicamentos/instrumentação , Eletroquímica/instrumentação , Eletroquímica/métodos , Indústrias/instrumentação , Teste de Materiais , Nanoestruturas/análise , Nanoestruturas/ultraestrutura , Nanotecnologia/instrumentação , Tamanho da Partícula , Polímeros/análise , Pesquisa , Propriedades de SuperfícieRESUMO
A parallel solution-phase library synthesis of functionalized diaminobenzamides is described. The four-step library synthesis is accomplished using polymer-assisted solution-phase (PASP) synthesis techniques. This high-yielding, multi-step sequence utilizes sequestering resins for the removal of reactants, reactant by-products, and employs a resin capture/release strategy as a key library synthesis step. Step one of the sequence relies on the displacement of an activated fluoro-group from the aromatic ring of 1a, b with a variety of primary amines to introduce the first diversity position. Step two is hydrolysis of the benzoate ester to a benzoic acid which is subsequently captured on a polyamine resin, washed, and released to give 4a, b in pure form. Step three utilizes PASP resins to mediate the amide coupling of a benzoic acid with a variety of primary amines to give the aminonitrobenzamides 5a, b and introduces the second diversity position. Step four is the parallel reduction of the aminonitrobenzamides 5a, b to the functionalized diaminobenzamides 6a, b. This library synthesis proceeds with high overall purities which average 80 % over the 4-step sequence.
Assuntos
Benzamidas/síntese química , Técnicas de Química Combinatória/métodos , Aminas/síntese química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Estrutura Molecular , Polímeros/químicaRESUMO
A functional polyacrylic acid (PAA) adsorbent has been prepared for metal chelate affinity chromatography. It has been found to chelate nickel ion Ni2+ strongly, and was evaluated for the ability to bind proteins containing neighbouring histidine residues. The principle of the technique was illustrated with Aeromonas hydrophila outer membrane protein OmpTS. DNA elements coding for adjacent histidines were fused to the Aeromonas hydrophila ompTS gene. Subsequent expression in E. coli resulted in the production of hybrid protein His6-OmpTS that could be purified by Ni2+-PAA affinity chromatography. The remarkable specificity found makes it an attractive addition to the range of adsorbents for metal chelate affinity chromatography.
Assuntos
Proteínas da Membrana Bacteriana Externa/isolamento & purificação , Cromatografia de Afinidade/métodos , Polímeros/química , Adsorção , Aeromonas/química , Sequência de Aminoácidos , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Sequência de Bases , DNA , Eletroforese em Gel de Poliacrilamida , Dados de Sequência Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Espectrofotometria InfravermelhoRESUMO
Surface entrapment is a convenient method to immobilize the natural macromolecules on the surface of synthetic polymers. In this study, the gelatin modified and sodium alginate/gelatin modified PLGA nanofibrous membranes were fabricated via surface entrapment and entrapment-graft techniques. The surface morphology of the each single modified PLGA nanofiber was as smooth as that of untreated PLGA nanofibers. The results of water angle contact measurements and tensile tests showed that the surface entrapment cannot only improve the hydrophilicity but also enhance mechanical properties of the modified nanofibrous membranes. In addition, the sodium alginate/gelatin modified electrospun PLGA nanofibrous membrane exhibited higher hydrophilicity and better biocompatibility than the simply gelatin modified PLGA nanofibrous membrane, which suggested the surface entrapment is a facile and efficient approach to surface modification for electrospun nanofibours membranes.
Assuntos
Materiais Biocompatíveis/química , Ácido Láctico/química , Nanofibras/química , Ácido Poliglicólico/química , Engenharia Tecidual/métodos , Alginatos/química , Técnicas Eletroquímicas , Gelatina/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Microscopia Eletrônica de Varredura , Nanofibras/ultraestrutura , Nanotecnologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Propriedades de Superfície , Resistência à TraçãoRESUMO
Using in situ high-pressure x-ray diffraction (XRD), we observed a pressure-induced polyamorphic transition from the low-density amorphous (LDA) state to the high-density amorphous (HDA) state in Ce(75)Al(23)Si(2) metallic glass at about 2 GPa and 300 K. The thermal stabilities of both LDA and HDA metallic glasses were further investigated using in situ high-temperature and high-pressure XRD, which revealed different pressure dependences of the onset crystallization temperature (T(x)) between them with a turning point at about 2 GPa. Compared with Ce(75)Al(25) metallic glass, minor Si doping shifts the onset polyamorphic transition pressure from 1.5 to 2 GPa and obviously stabilizes both LDA and HDA metallic glasses with higher T(x) and changes their slopes dT(x)/dP. The results obtained in this work reveal another polyamorphous metallic glass system by minor alloying (e.g. Si), which could modify the transition pressure and also properties of LDA and HDA metallic glasses. The minor alloying effect reported here is valuable for the development of more polyamorphous metallic glasses, even multicomponent bulk metallic glasses with modified properties, which will trigger more investigations in this field and improve our understanding of polyamorphism and metallic glasses.
Assuntos
Ligas/química , Vidro/química , Difração de Raios X/métodos , Alumínio/química , Césio/química , Cristalização/métodos , Pressão , Silício/química , TemperaturaRESUMO
To evaluate the parental craniofacial morphology in Chinese patients with sporadic nonsyndromic cleft palate, 175 parental pairs of children with nonsyndromic cleft palate (NSCP) and 206 controls from Sichuan University were involved in this study. Conventional cephalometric analysis was used to measure angles, linear distances and their ratios. Two-sample Student's t-tests and multivariate discriminant analysis were applied to the data. The data indicated that fathers of children with NSCP tended to have longer anterior cranial base length, palatal length, mandibular body length, mandibular ramus length, and longer mandibular height, lower face height, as well as larger nasal width, palatal width, mandibular body width, and condyle distance (p<0.05). Mothers of children with NSCP tended to have longer mandibular body length, mandibular ramus length, and longer mandibular height, lower face height, as well as larger nasal width, palatal width, mandibular body width, and condyle distance (p<0.05). The results indicated that the healthy parents of the patients with NSCP show distinct characteristics in craniofacial morphology. In general, the characteristics seem to be more distinct in the fathers of cleft patients than in the mothers.
Assuntos
Fissura Palatina/genética , Ossos Faciais/anatomia & histologia , Predisposição Genética para Doença , Desenvolvimento Maxilofacial/genética , Pais , Adulto , Povo Asiático , Estudos de Casos e Controles , Cefalometria/estatística & dados numéricos , China , Análise Discriminante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Base do Crânio/anatomia & histologiaRESUMO
The major challenge in the development of anti-schistosome vaccines is to use defined antigens to stimulate an appropriate immune response that leads to resistance. Several promising candidate vaccine antigens including the glycolytic enzyme triose-phosphate isomerase (SmTPI), a 28 kDa glutathione-S-transferase (Sm28), the myofibrilar protein paramyosin (Sm97), an integral membrane protein (Sm23) and calpain (Smcalpain) have been characterised and their primary sequences derived for Schistosoma mansoni. Furthermore, sequences are available for synthetic peptides mimicking epitopes on these molecules capable of inducing schistosome-specific T- and B-cell responses. These schistosome vaccine candidates have generally been tested with varying degrees of success as single components, with only one report of the use of a multivalent antigen or multi-epitope approach. We describe the assembly of multiple defined and different epitopes of S. mansoni into a variety of single covalent structures; these included a DNA vaccine encoding different epitopes in tandem, the polyprotein itself that is encoded by this DNA and branched synthetic peptide epitope-based polymers in which the individual epitopes are pendant from an inert backbone. Each of the vaccine constructs examined, with the exception of the DNA vaccine, generated antibodies that were capable of binding to a tandem sequence of the epitopes. Although these results were encouraging, none of the constructs protected animals from subsequent challenge infection, indicating that the immune responses elicited were inadequate or inappropriate for parasite killing in vivo.
Assuntos
DNA de Helmintos/administração & dosagem , Proteínas de Helminto/administração & dosagem , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas/administração & dosagem , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , DNA de Helmintos/imunologia , Epitopos , Feminino , Proteínas de Helminto/imunologia , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Plasmídeos/genética , Polímeros/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Schistosoma mansoni/genética , Esquistossomose mansoni/imunologia , Vacinas/imunologiaRESUMO
Field cancerization predisposes the upper aerodigestive tract mucosa to the formation of multiple primary tumors, when exposed to environmental carcinogens. Up-regulation of epidermal growth factor receptor occurs early in squamous cell carcinogenesis and is critical for the loss of growth control in a variety of human cancers, including head and neck squamous cell carcinomas. In these tumor cells in culture, epidermal growth factor receptor stimulation initiates signaling via persistent activation of selective STAT proteins. To determine the timing of Stat3 activation in head and neck carcinogenesis, we studied the expression and constitutive activation of Stat3 in tumors and normal mucosa from patients with head and neck cancer compared with mucosa from controls without cancer. Stat3 was up-regulated and constitutively activated in both primary human head and neck tumors as well as in normal mucosa from these cancer patients compared with control normal mucosa from patients without cancer. In vivo liposome-mediated gene therapy with a Stat3 antisense plasmid efficiently inhibited Stat3 activation, increased tumor cell apoptosis, and decreased Bcl-x(L) expression in a head and neck xenograft model. These findings provide evidence that constitutively activated Stat3 is an early event in head and neck carcinogenesis that contributes to the loss of growth control by an anti-apoptotic mechanism.